The role of type 1 interferons in coagulation induced by gram-negative bacteria

Blood. 2020 Apr 2;135(14):1087-1100. doi: 10.1182/blood.2019002282.


Bacterial infection not only stimulates innate immune responses but also activates coagulation cascades. Overactivation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), a widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC by amplifying the release of high-mobility group box 1 (HMGB1) into the bloodstream. Inhibition of the expression of type 1 IFNs and disruption of their receptor IFN-α/βR or downstream effector (eg, HMGB1) uniformly decreased gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the procoagulant activity of tissue factor by promoting the externalization of phosphatidylserine to the outer cell surface, where phosphatidylserine assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but they also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / immunology
  • Animals
  • Blood Coagulation
  • Disseminated Intravascular Coagulation / blood
  • Disseminated Intravascular Coagulation / etiology
  • Disseminated Intravascular Coagulation / immunology*
  • Endotoxemia / blood
  • Endotoxemia / complications
  • Endotoxemia / immunology*
  • Gram-Negative Bacteria / immunology*
  • Gram-Negative Bacterial Infections / blood
  • Gram-Negative Bacterial Infections / complications
  • Gram-Negative Bacterial Infections / immunology*
  • HMGB1 Protein / blood
  • HMGB1 Protein / immunology
  • Humans
  • Immunity, Innate
  • Interferon-alpha / immunology*
  • Interferon-beta / immunology*
  • Mice, Inbred C57BL


  • Adaptor Proteins, Vesicular Transport
  • HMGB1 Protein
  • Interferon-alpha
  • TICAM-1 protein, mouse
  • Interferon-beta